The influence of acceptor nucleophilicity on the glycosylation reaction mechanism

The acceptor dependence on the glycosylation stereoselectivity is revealed by a systematic study employing model acceptors of gradually changing nucleophilicity.

Spectroscopic data were in accord with those previously reported. 6

S4
To a 140°C solution of NaOAc (8.2 g, 100 mmol, 0.5 eq) in Ac2O (190 mL, 2 mol, 10 eq.) D-glucose was added portionwise and the reaction mixture was refluxed for an additional 15 min. The solution was cooled to r.t. and poured over crushed ice.

Phenyl 1-thio-β-D-glucopyranoside (S5)
To a solution of S4 (16.3 g, 37.0 mmol) in MeOH (200 mL) was added Na(s) (89 mg, 3.7 mmol, 0.1 eq) and the reaction was stirred for 18 h at r.t. The reaction mixture was neutralized with Amberlite H + , filtered and Celite® was added to the filtrate and the mixture concentrated in vacuo. The residue was purified by flash column chromatography (1% to 12% EtOH in EtOAc) to obtain a white solid (8.6 g, 31.6 mmol, 85%). Spectroscopic data were in accord with those previously reported. 15
The resulting organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The crude product S9 was suspended in MeOH (100 mL) followed by the addition of p-TsOH·H2O (0.19 g, 1 mmol, 0.1 eq.). After stirring for 1 h at 50 ⁰C the reaction mixture was quenched with sat. aq. NaHCO3 and concentrated in vacuo. Flash column chromatography (1/0 to 7/3 pentane/EtOAc) afforded the title compound as a waxy solid (3.6 g, 7.7 mmol, 78% over 3 steps). Spectroscopic data were in accord with those previously reported. 11,18 Rf: 0.57 (7/
Spectroscopic data were in accord with those previously reported. 11
Spectroscopic data were in accord with those previously reported. 11

S10
Fully protected S11 (9.25 g, 20 mmol) and p-TsOH•H2O (380 mg, 2 mmol, 0.1 eq.) were added to MeOH (100 mL) and heated at 60°C for 15 min after all solids were dissolved and TLC analysis showed full conversion to a lower running spot. The reaction mixture was quenched with Et3N (1 mL) and concentrated in vacuo. The crude product was purified by flash column chromatography (8/1 to 3/2 pentane/acetone) to give the tile compound as a white solid (7.4 g, 19.8
Spectroscopic data were in accord with those previously reported. 21
After 30 min Amberlite H + was added until neutral pH was achieved and the resin was subsequently filtered off. The solution S12 was concentrated in vacuo to give the crude tetra-ol. Spectroscopic data were in accord with those previously reported. 25  Hz, H-2); 13